Effects of oxidised low density lipoprotein on dendritic cells: a possible immunoregulatory component of the atherogenic micro-environment?

Alderman, Charles; Bunyard, Peter; Chain, Benjamin M.; Foreman, J. C.; Leake, David S.; Katz, David R.

doi:10.1016/s0008-6363(02)00447-9

Cited by 101 publications

(79 citation statements)

References 43 publications

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“…Oxidative stress induced by reactive oxygen species in CSE may also impair DC-T cell communication. However, oxidized protein products have been reported to enhance, rather than suppress DC function (31)(32)(33). The diminished priming capacity of CSE-conditioned DCs may also result from alterations in the activity of transcription factors like NF-B or AP-1 (34 -36).…”

Section: Discussionmentioning

confidence: 99%

Cigarette Smoke Extract Suppresses Human Dendritic Cell Function Leading to Preferential Induction of Th-2 Priming

Vassallo¹,

Tamada

Lau

et al. 2005

The Journal of Immunology

188

170

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Dendritic cells (DC) are key regulators of immune responses. In the current study, we hypothesized that cigarette smoke-induced aberrance in DC function is an important mechanism by which smokers develop cancer, infection, and allergy—diseases common in smokers. We demonstrate that cigarette smoke extract (CSE) inhibits DC-mediated priming of T cells, specifically inhibiting the secretion of IFN-γ whereas enhancing the production of IL-4 in the MLR. Conditioning with CSE did not effect cytokine (IL-10, IL-6, or IL-12) production from immature DCs, but significantly inhibited IL-12p70 release by LPS-matured DCs. In contrast, IL-10 secretion by LPS-activated CSE-conditioned DCs was enhanced when compared with control DCs. CSE also induced cyclooxygenase-2 protein levels in maturing DCs and significantly augmented endogenous PGE2 release. Conditioning of DCs with CSE also suppressed LPS-mediated induction of CD40, CD80, and CD86, and suppressed maturation-associated CCR7 expression. Although CSE has been reported to induce apoptosis of fibroblasts and epithelial cells, the immunomodulatory effects observed with CSE were not due to diminished DC viability. The effects of CSE on DC function were not exclusively mediated by nicotine, because equivalent, or even higher concentrations of nicotine than those found in CSE, failed to suppress DC-induced T cell priming. These data provide evidence that soluble components extracted from cigarette smoke suppress key DC functions and favor the development of Th-2 immunity.

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Section: Discussionmentioning

confidence: 99%

Cigarette Smoke Extract Suppresses Human Dendritic Cell Function Leading to Preferential Induction of Th-2 Priming

Vassallo¹,

Tamada

Lau

et al. 2005

The Journal of Immunology

188

170

View full text Add to dashboard Cite

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“…Adherent monocytes were cultured for 7-8 days in GM-CSF and IL-4. Residual monocytes/lymphocytes were removed by magnetic bead depletion after 4 days as described in detail elsewhere (10). Resulting DC were Ͼ90% CD1a ϩ , CD13 ϩ , CD14 low , and HLA-DR high .…”

Section: Dendritic Cellsmentioning

confidence: 99%

“…Phenotypic analysis of DC was conducted using standard methods as described previously (10). For intracellular staining, DC were fixed in 4% paraformaldehyde on ice for 10 min and then permeabilized in 0.1% Triton X-100 on ice for 10 min.…”

Section: Flow Cytometrymentioning

confidence: 99%

The Expression and Function of Cathepsin E in Dendritic Cells

Chain¹,

Free

Medd³

et al. 2005

The Journal of Immunology

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Cathepsin E is an aspartic proteinase that has been implicated in Ag processing within the class II MHC pathway. In this study, we document the presence of cathepsin E message and protein in human myeloid dendritic cells, the preeminent APCs of the immune system. Cathepsin E is found in a perinuclear compartment, which is likely to form part of the endoplasmic reticulum, and also a peripheral compartment just beneath the cell membrane, with a similar distribution to that of Texas Red-dextran within 2 min of endocytosis. To investigate the function of cathepsin E in processing, a new soluble targeted inhibitor was synthesized by linking the microbial aspartic proteinase inhibitor pepstatin to mannosylated BSA via a cleavable disulfide linker. This inhibitor was shown to block cathepsin D/E activity in cell-free assays and within dendritic cells. The inhibitor blocked the ability of dendritic cells from wild-type as well as cathepsin D-deficient mice to present intact OVA, but not an OVA-derived peptide, to cognate T cells. The data therefore support the hypothesis that cathepsin E has an important nonredundant role in the class II MHC Ag processing pathway within dendritic cells.

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“…Oxidized low-density lipoprotein (LDL) can also promote the maturation of DCs from monocyte precursors and causes the down-regulation of interleukin (IL)-12 production in DCs. [11][12][13] DCs are also early participants in developing diabetic lesions before the appearance of scavenger macrophages, 14 and DCs are present in atherosclerotic arteries. 15 To test the hypothesis that DCs may acquire fat and glycogen stores during development, we studied DCs developing from mouse bone marrow stem cells with and without increasing doses of IL-4 or lipopolysaccharide (LPS), both of which promote the stimulatory ability of DCs for T cells.…”

Section: M M U N O L O G Y O R I G I N a L A R T I C L Ementioning

confidence: 99%

Developing dendritic cells become ‘lacy’ cells packed with fat and glycogen

Maroof¹,

English²,

Bedford³

et al. 2005

Immunology

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SummaryOn maturation, dendritic cells (DCs) become highly active cells equipped for antigen uptake, migration and clustering and activation of T cells. We therefore asked whether DCs acquire fat and glycogen stores as they mature. DCs were generated from mouse bone marrow stem cells by culturing with granulocyte-macrophage colony-stimulating factor (GM-CSF) for 7-8 days. Stimulation of the DCs with lipopolysaccharide (LPS) for the last 24 hr of culture, or exposure to 1-15 ng/ml of interleukin (IL)-4 during development, resulted in production of DCs not only with an increased ability to stimulate T cells but also with an increasingly lacy appearance on transmission electron microscopy, with multiple unstained areas in the cytoplasm. This changed morphology was associated with the presence of increasing amounts of fat and glycogen, identified by Sudan Black and periodic acid leukofushin/Schiff (PAS) staining, respectively. Lacy DCs up-regulated type 1 and type 2 scavenger receptors, providing possible mechanisms contributing to these changes. Lacy DCs were found occasionally amongst freshly isolated splenic and lymph node DCs. DCs can be isolated from human adipose tissue, and we tested whether lacy DCs acquiring fat and glycogen were present in mouse omentum. CD45 + cells migrating from the omentum expressed specific DC markers CD11c and 33D1, costimulatory molecules and major histocompatibility complex (MHC) class II, and most showed darkly staining fat inclusions. Thus, during development, DCs can acquire large amounts of fat and glycogen, accumulation of which is promoted by antigen exposure and modulated by the cytokine milieu and location, and which may act as a link between energy stores and immune function.

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Effects of oxidised low density lipoprotein on dendritic cells: a possible immunoregulatory component of the atherogenic micro-environment?

Cited by 101 publications

References 43 publications

Cigarette Smoke Extract Suppresses Human Dendritic Cell Function Leading to Preferential Induction of Th-2 Priming

Cigarette Smoke Extract Suppresses Human Dendritic Cell Function Leading to Preferential Induction of Th-2 Priming

The Expression and Function of Cathepsin E in Dendritic Cells

Developing dendritic cells become ‘lacy’ cells packed with fat and glycogen

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